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Diabetes 53:2392-2396, 2004
© 2004 by the American Diabetes Association, Inc.

Increased Expression of Gi-Coupled Muscarinic Acetylcholine Receptor and Gi in Atrium of Elderly Diabetic Subjects

Mark D. Richardson1, Jason D. Kilts1, and Madan M. Kwatra1,,2,,3

1 Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina
2 Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina
3 Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina

In an ongoing investigation of the effects of age on G protein–coupled receptor signaling in human atrial tissue, we have found that the density of atrial muscarinic acetylcholine receptor (mAChR) increases with age but reaches statistical significance only in patients with diabetes. Moreover, we find that in elderly subjects of similar ages, those with diabetes have 1.7-fold higher levels of G{alpha}i2 and twofold higher levels of Gß1. Diabetes does not affect other atrial G proteins, including G{alpha}i3, G{alpha}s, G{alpha}o, and Gß2. These data represent the first demonstration of an increase in a Gi-coupled receptor, G{alpha}i2, and Gß1, in atrium of patients with diabetes. These findings suggest a molecular explanation for the increased risk of cardiac disease in patients with diabetes, because increased signaling through Gi has been shown to lead to the development of dilated cardiomyopathy.

Address correspondence and reprint requests to Madan M. Kwatra, PhD, Box 3094, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710. E-mail: kwatr001{at}mc.duke.edu


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Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.